ENDOMETRIOSIS-ASSOCIATED SECRETORY PROTEINS

子宫内膜异位症是一种疾病，导致衰弱的疼痛和损失的 妇女的生育能力。 尽管有这些破坏性的影响， 这种神秘的疾病发挥这些致病性是未知的。 虽然在组织学上与子宫内膜相似， 组织在生物化学上不同于其子宫对应物， 各种各样的时尚。 改变的生化特性， 增生组织可能与免疫系统的异常有关， 排卵、受精和着床，这些都与 是导致子宫内膜异位症相关不孕的原因 使用子宫内膜异位症的大鼠模型， 已经鉴定了与糖尿病相关的蛋白质。 黄体酮- 诱导子宫蛋白PUP-1可能在正常生殖过程中发挥作用， 包括植入在内的过程。 奇怪的是，合成和/或分泌 PUP-1的植入是24小时的相位与 子宫内膜 第二种蛋白质EP-1是通过以下途径合成的： 子宫内膜增生但不是子宫内膜组织。 EP-1可能是一个有用的标记物 在子宫内膜异位症的病理生理学中起作用。 PUP-1和EP-1最近已在来自 纯化的大鼠和人子宫内膜和子宫内膜异位症植入基质 细胞，分别。 该提案的目标是纯化和表征大鼠和 人PUP-1和EP-1，以便深入了解其结构、模式 这些蛋白质的表达和生理功能。 具体 本项目的目标是：1）开发PUP-1的纯化方案 和EP-1; 2）产生a）抗血清，B）放射免疫测定和c）有限的 PUP-1和EP-1的蛋白质序列数据;和3）分子克隆cDNA 代表PUP-1和EP-1并获得核苷酸序列数据。 蛋白质纯化将采用细胞培养和色谱法。 技术. 抗血清、放射免疫测定和蛋白质序列数据 从纯化的蛋白质衍生的将用于检测和监测 PUP-1和EP-1在各种组织和血清中的分布 生殖周期、怀孕早期和使用类固醇后 处理以及获得PUP-1和EP-1的DNA序列数据。 的 将核酸序列数据与其它序列信息进行比较 在数据库中，以提供对身份的进一步了解， 蛋白质的功能。 这些研究将支持长期目标，包括确定 PUP-1和EP-1在生殖功能和病理生理中的作用 子宫内膜异位症 PUP-1和EP-1的表征也可能导致 开发非侵入性的孕酮血清标记物- 依赖性子宫内膜功能和疾病子宫内膜异位症。 最终，这些研究可能会改善诊断、预后和 子宫内膜异位症的治疗方法。

Endometriosis is a disease that causes debilitating pain and loss of fertility in women. Despite these devastating effects, the mechanism by which this enigmatic disease exerts these pathogenicities is unknown. Although histologically similar to uterine endometrium, endometriotic tissue is biochemically different from its uterine counterpart in a variety of fashions. The altered biochemical characteristics of the endometriotic tissue may be involved with anomalies of the immune system, ovulation, fertilization, and implantation which have all been implicated as causes of endometriosis-associated infertility. Using a rat model for endometriosis, two previously unknown endometriosis-associated proteins have been identified. A progesterone- induced uterine protein, PUP-1, may play a role in normal reproductive processes including implantation. Curiously, synthesis and/or secretion of PUP-1 by the endometriotic implant is 24 hours out of phase with that of the uterine endometrium. A second protein, EP-1, is synthesized by endometriotic but not endometrial tissue. EP-1 may be a useful marker of endometriosis and have a role in the pathophysiology of the disease. PUP-1 and EP-1 have recently been identified in culture media from purified rat and human endometrial and endometriotic implant stromal cells, respectively. The goal of this proposal is to purify and characterize both rat and human PUP-1 and EP-1 in order to obtain insight into the structure, mode of expression and physiological function of these proteins. The specific aims of this project are to: 1) develop a purification scheme for PUP-1 and EP-1; 2) generate a) antisera, b) radioimmunoassays and c) limited protein sequence data for PUP-1 and EP-1; and 3) molecularly clone cDNA representing PUP-1 and EP-1 and obtain nucleotide sequence data. Protein purification will employ cell culture and chromatographic techniques. the antisera, radioimmunoassays and protein sequence data derived from the purified proteins will be used to detect and monitor the distribution of PUP-1 and EP-1 in various tissues and in sera throughout the reproductive cycle, during early pregnancy and following steroid treatment as well as to obtain DNA sequence data for PUP-1 and EP-1. The nucleic acid sequence data will be compared to other sequence information in data banks to provide further insight into the identity and possible function of the proteins. These studies will support long term goals which include determining the role of PUP-1 and EP-1 in reproductive function and the pathophysiology of endometriosis. The characterization of PUP-1 and EP-1 may also lead to the development of non-invasive serum markers for progesterone- dependent endometrial function and the disease endometriosis. Ultimately, these studies may lead to improved diagnostic, prognostic and therapeutic methods for the management of endometriosis.